Biology subjects

Jia, B. Z.

Publications and source records attributed to Jia, B. Z..

8 recordsLinked to original sources

bioRxiv2026

Mapping absolute membrane voltage using dynamic photocycle control

Fluorescent voltage indicators are widely used to report relative changes in membrane potential, but mapping absolute voltages remains difficult. Here we present Voltage Measurement by Activated Photocycles (VMAP), a simple method for absolute voltage imaging based on a photophysical switch between voltage-insensitive and sensitive indicator states. VMAP requires no specialized hardware or additional labeling, and is applicable across species, sample preparations, and microscope configurations. Using VMAP, we quantified drug-induced shifts in neuronal resting potential, revealed the emergence of bioelectric patterns during multi-day recordings of human iPSC populations, and created 3D membrane-potential maps across whole live zebrafish embryos. By making absolute voltage imaging accessible from cellular to organismal scales and from milliseconds to days, VMAP opens a route to mapping bioelectrical organization in complex living systems.

biophysics↗

bioRxiv2025

Luminos: open-source software for bidirectional microscopy

Bidirectional microscopy (BDM) combines simultaneous targeted optical perturbation and imaging of biophysical or biochemical signals (e.g. membrane voltage, Ca2+, or signaling molecules). A core challenge in BDM is precise spatial and temporal alignment of stimulation, imaging, and other experimental parameters. Here we present Luminos, an open-source MATLAB library for modular and precisely synchronized control of BDM experiments. The system supports hardware-triggered synchronization across stimulation, recording, and imaging channels with microsecond accuracy. Source code and documentation for Luminos are available online at https://www.luminosmicroscopy.com and https://github.com/adamcohenlab/luminos-microscopy. This library will facilitate development of bidirectional microscopy methods across the biological sciences.

bioengineering↗

bioRxiv2025

Swimming motions evoke Ca2+ events in vascular endothelial cells of larval zebrafish via mechanical activation of Piezo1

Calcium signaling in blood vessels regulates their growth1,2, immune response3, and vascular tone4. Vascular endothelial cells are known to be mechanosensitive5-7, and it has been assumed that this mechanosensation mediates calcium responses to pulsatile blood flow8-10. Here we show that in larval zebrafish, the dominant trigger for vascular endothelial Ca2+ events comes from body motion, not heartbeat-driven blood flow. Through a series of pharmacological and mechanical perturbations, we showed that body motion is necessary and sufficient to induce endothelial Ca2+ events, while neither neural activity nor blood circulation is either necessary or sufficient. Knockout and temporally restricted knockdown of piezo1 eliminated the motion-induced Ca2+ events. Our results demonstrate that swimming-induced tissue motion is an important driver of endothelial Ca2+ dynamics in larval zebrafish. HighlightsO_LISwimming motions in larval zebrafish evoke large, rapid, and pervasive Ca2+ transients in vascular endothelial cells. C_LIO_LIThese Ca2+ transients do not require neural firing, muscular electrical activity, endocrine factors, or heart-driven blood flow. C_LIO_LIMechanical forces are necessary and sufficient for endothelial Ca2+ transients. C_LIO_LIEndothelial Ca2+ transients require the mechanosensitive ion channel Piezo1. C_LI

physiology↗

bioRxiv2025

Neural plate pre-patterning enables specification of intermediate neural progenitors in the spinal cord

Spinal cord organization begins with the specification of a series of neural progenitor domains along the dorsal-ventral axis of the neural tube. Patterning at the dorsal and ventral ends is established by canonical morphogen gradients. Intermediate progenitor domains are located distally to morphogen sources yet display similar organization. How this is achieved is unclear and the relevant positional cues have not been identified. Here we show that intermediate progenitor domains are established through a distinct mechanism that operates in the preceding neural plate stage and leverages its multiple signaling inputs and morphogenesis. An integrated spatial atlas of transcription factor expression, signaling activity, and cell movement reveals that the neural plate comprises an array of cell states, defined by combinatorial signaling and morphogenesis-driven transitions between local signaling environments. Specifically, we find that p0 and p1 intermediate progenitors, located immediately outside the morphogen-patterned region, arise from specific precursor states that are established in the posterior neural plate by tailbud-derived Wnt signaling. Convergent-extension movements subsequently drive progenitor specification by displacing precursors out of Wnt/FGF signaling fields while shaping them into stripe-like domains. Thus, by controlling signaling exposure, tissue dynamics convert positional information encoded by signaling history into downstream fate specification. This mode of patterning may operate broadly across developmental contexts, with implications for tissue engineering and patterning-related disorders.

developmental biology↗

bioRxiv2024

Zebrafish glial-vascular interactions progressively expand over the course of brain development

Glial-vascular interactions are critical for the formation and maintenance of brain blood vessels and the blood-brain barrier (BBB) in mammals, but their role in zebrafish is not well understood. Our previous work has detailed the timeline of BBB functional maturation in zebrafish, revealing a conserved mechanism of BBB induction through the suppression of endothelial transcytosis. Yet, as opposed to extensive research on glial-vascular interactions in rodents, such interactions remain largely overlooked in the zebrafish model system. Here, we focus on glial-vascular development in the zebrafish brain, leveraging three glial gene promoters: gfap (glial fibrillary acidic protein), glast (an astrocyte-specific glutamate transporter), and glastini (a new, shortened, equally effective version of the Glast promoter). Using these glial promoters, sparse labeling revealed fewer glial-vascular interactions during early larval stages, with both glial coverage and contact area increasing as the zebrafish brain matured. We then generated stable transgenic lines for both the Glast and Glastini promoters and observed similar increases in glial coverage during larval development, starting at [~]30% coverage at 3 days post-fertilization (dpf) and peaking at [~]60% at 10 dpf. Ultrastructural assessment of glial-vascular interactions using electron microscopy (EM) confirmed a progressive increase in glial coverage over larval development, with maximal coverage reaching [~]70% in adult zebrafish, significantly lower than the nearly 100% coverage observed in mammals. Finally, immunogold-EM labeling confirmed that cells identified as glia in aforementioned morphological analyses were indeed Glast-positive. Taken together, our results identify the temporal profile of glial-vascular maturation in the zebrafish brain.

developmental biology↗

bioRxiv2024

Optogenetic control of Nodal signaling patterns

A crucial step in early embryogenesis is the establishment of spatial patterns of signaling activity. Tools to perturb morphogen signals with high resolution in space and time can help reveal how embryonic cells decode these signals to make appropriate fate decisions. Here, we present new optogenetic reagents and an experimental pipeline for creating designer Nodal signaling patterns in live zebrafish embryos. Nodal receptors were fused to the light-sensitive heterodimerizing pair Cry2/CIB1N, and the Type II receptor was sequestered to the cytosol. The improved optoNodal2 reagents eliminate dark activity and improve response kinetics, without sacrificing dynamic range. We adapted an ultra-widefield microscopy platform for parallel light patterning in up to 36 embryos and demonstrated precise spatial control over Nodal signaling activity and downstream gene expression. Patterned Nodal activation drove precisely controlled internalization of endodermal precursors. Further, we used patterned illumination to generate synthetic signaling patterns in Nodal signaling mutants, rescuing several characteristic developmental defects. This study establishes an experimental toolkit for systematic exploration of Nodal signaling patterns in live embryos.

developmental biology↗

bioRxiv2022

A bioelectrical phase transition patterns the first beats of a vertebrate heart

The heart is among the first organs to function in vertebrate development, but its transition from silent to beating has not been directly characterized. Using all-optical electrophysiology, we captured the very first zebrafish heartbeat and analyzed the development of cardiac excitability around this singular event. The first beats appeared suddenly and propagated coherently across the primordial heart. Targeted optogenetic perturbations mapped the development of excitability and conduction before and after the first heartbeats. Measured bioelectrical dynamics support a noisy saddle-node on invariant circle (SNIC) bifurcation as the critical phase transition that starts the heart. Simple models of this bifurcation quantitatively capture cardiac dynamics in space and time through early development, including coherent beating before transcriptional specification of pacemakers. Our work shows how gradual and largely asynchronous development of single-cell bioelectrical properties produces a stereotyped and robust tissue-scale transition from quiescence to coordinated beating.

developmental biology↗

bioRxiv2020

Spatial heterogeneity of cell-matrix adhesive forces predicts human glioblastoma migration

BackgroundGlioblastoma (GBM) is a highly aggressive incurable brain tumor. The main cause of mortality in GBM patients is the invasive rim of cells migrating away from the main tumor mass and invading healthy parts of the brain. Although motion is driven by forces, our current understanding of the physical factors involved in glioma infiltration remains limited. This study aims to investigate the adhesion properties within and between patients tumors on a cellular level and test whether these properties correlate with cell migration. MethodsNine tissue samples were taken from spatially separated sections during 5-aminolevulinic acid (5-ALA) fluorescence guided surgery. Navigated biopsy samples were collected from strongly fluorescent tumor cores, a weak fluorescent tumor rim, and non-fluorescent tumor margins. A microfluidics device was built to induce controlled shear forces to detach cells from monolayer cultures. Cells were cultured on low modulus polydimethylsiloxane representative of the stiffness of brain tissue. Cell migration and morphology were then obtained using time lapse microscopy. ResultsGBM cell populations from different tumor fractions of the same patient exhibited different migratory and adhesive behaviors. These differences were associated with sampling location and amount of 5-ALA fluorescence. Cells derived from weak- and non-fluorescent tumor tissue were smaller, adhered less well, and migrated quicker than cells derived from strongly fluorescent tumor mass. ConclusionGBM tumors are biomechanically heterogeneous. Selecting multiple populations and broad location sampling are therefore important to consider for drug testing. Key pointsGBM tumors are biomechanically heterogeneous GBM cell migration is inversely correlated with cell-matrix adhesion strength 5-ALA fluorescence intensity during surgery correlates with the motility properties of GBM cells Importance of the studyThis is the first study to compare single cell migration and cell-matrix adhesion strength of GBM, using cell lines derived from different tumors and from different regions within the same tumor. Not accounting for internal sampling location within each tumor obscures differences in cell morphology, motility and adhesion properties between patients. Peripherical and marginal tumor cells have different adhesion profiles and are highly migratory compared to those found in the core of the tumor. Aggressive regions of the tumor (highly motile) are linked to the spatial distribution of adhesion strength and are strongly associated with 5-ALA fluorescence intensity. Preclinical tests aimed at developing a treatment for GBM using anti-invasive drugs or adhesion inhibitors, would benefit from using cell lines derived from the tumor periphery (with low 5-ALA intensity) rather than cell lines derived from the tumor core.

biophysics↗